Salmonella typhimurium LT2 catabolizes propionate via the 2-methylcitric acid cycle

J Bacteriol. 1999 Sep;181(18):5615-23. doi: 10.1128/JB.181.18.5615-5623.1999.


We previously identified the prpBCDE operon, which encodes catabolic functions required for propionate catabolism in Salmonella typhimurium. Results from (13)C-labeling experiments have identified the route of propionate breakdown and determined the biochemical role of each Prp enzyme in this pathway. The identification of catabolites accumulating in wild-type and mutant strains was consistent with propionate breakdown through the 2-methylcitric acid cycle. Our experiments demonstrate that the alpha-carbon of propionate is oxidized to yield pyruvate. The reactions are catalyzed by propionyl coenzyme A (propionyl-CoA) synthetase (PrpE), 2-methylcitrate synthase (PrpC), 2-methylcitrate dehydratase (probably PrpD), 2-methylisocitrate hydratase (probably PrpD), and 2-methylisocitrate lyase (PrpB). In support of this conclusion, the PrpC enzyme was purified to homogeneity and shown to have 2-methylcitrate synthase activity in vitro. (1)H nuclear magnetic resonance spectroscopy and negative-ion electrospray ionization mass spectrometry identified 2-methylcitrate as the product of the PrpC reaction. Although PrpC could use acetyl-CoA as a substrate to synthesize citrate, kinetic analysis demonstrated that propionyl-CoA is the preferred substrate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbon Isotopes
  • Citrate (si)-Synthase / metabolism
  • Citrates / metabolism
  • Genotype
  • Isocitrates / metabolism
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Models, Chemical
  • Operon
  • Oxo-Acid-Lyases / metabolism
  • Propionates / metabolism*
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism*


  • Carbon Isotopes
  • Citrates
  • Isocitrates
  • Propionates
  • threo-alpha-methylisocitrate
  • 2-methylcitric acid
  • Citrate (si)-Synthase
  • 2-methylcitrate synthase
  • Oxo-Acid-Lyases